People may face unique issues when it comes to substance use, as a result of both sex and gender. Sex differences result from biological factors, such as sex chromosomes and hormones, while gender differences are based on culturally defined roles for men and women, as well as those who do not identify with either category. Gender roles influence how people perceive themselves and how they interact with others. Sex and gender can also interact with each other to create even more complex differences among people. While the NIH is working to strengthen research on sex/gender differences across domains of health, current evidence is limited; for the purpose of this report, male and female subjects identify as such across both sex and gender.